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    Por favor, use este identificador para citar o enlazar este ítem: http://hdl.handle.net/10259/9790

    Título
    Nuclear FAK Controls Chemokine Transcription, Tregs, and Evasion of Anti-tumor Immunity
    Autor
    Serrels, Alan
    Lund, Tom
    Serrels, Bryan
    Byron, Adam
    McPherson, Rhoanne C.
    Kriegsheim, Alexander von
    Gómez Cuadrado, LauraAutoridad UBU Orcid
    Canel, Marta
    Muir, Morwenna
    Ring, Jennifer E.
    Maniati, Eleni
    Sims, Andrew H.
    Patcher, Jonathan A.
    Brunton, Valerie G.
    Gilbert, Nick
    Anderton, Stephen M.
    Nibbs, Robert J.B.
    Frame, Margaret C.
    Publicado en
    Cell. 2015, V. 163, n. 1, p. 160-173
    Editorial
    Elsevier
    Fecha de publicación
    2015-09
    ISSN
    0092-8674
    DOI
    10.1016/j.cell.2015.09.001
    Zusammenfassung
    Focal adhesion kinase (FAK) promotes anti-tumor immune evasion. Specifically, the kinase activity of nuclear-targeted FAK in squamous cell carcinoma (SCC) cells drives exhaustion of CD8+ T cells and recruitment of regulatory T cells (Tregs) in the tumor microenvironment by regulating chemokine/cytokine and ligand-receptor networks, including via transcription of Ccl5, which is crucial. These changes inhibit antigen-primed cytotoxic CD8+ T cell activity, permitting growth of FAK-expressing tumors. Mechanistically, nuclear FAK is associated with chromatin and exists in complex with transcription factors and their upstream regulators that control Ccl5 expression. Furthermore, FAK’s immuno-modulatory nuclear activities may be specific to cancerous squamous epithelial cells, as normal keratinocytes do not have nuclear FAK. Finally, we show that a small-molecule FAK kinase inhibitor, VS-4718, which is currently in clinical development, also drives depletion of Tregs and promotes a CD8+ T cell-mediated anti-tumor response. Therefore, FAK inhibitors may trigger immune-mediated tumor regression, providing previously unrecognized therapeutic opportunities.
    Materia
    Medicina
    Medicine
    Química orgánica
    Chemistry, Organic
    Salud
    Health
    URI
    http://hdl.handle.net/10259/9790
    Versión del editor
    https://doi.org/10.1016/j.cell.2015.09.001
    Aparece en las colecciones
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    Atribución 4.0 Internacional
    Documento(s) sujeto(s) a una licencia Creative Commons Atribución 4.0 Internacional
    Dateien zu dieser Ressource
    Nombre:
    serrels-cell_2015.pdf
    Tamaño:
    3.720Mb
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